Metabolic stress, IAPP and islet amyloid

作者：Montane J; Klimek Abercrombie A; Potter K J; Westwell Roper C; Verchere C Bruce^*

来源：Diabetes, Obesity and Metabolism, 2012, 14(s3): 68-77.

DOI：10.1111/j.1463-1326.2012.01657.x

• beta-cell
• amylin
• diabetes
• insulin

Amyloid forms within pancreatic islets in type 2 diabetes from aggregates of the beta-cell peptide islet amyloid polypeptide (IAPP). These aggregates are toxic to beta-cells, inducing beta-cell death and dysfunction, as well as inciting islet inflammation. The beta-cell is subject to a number of other stressors, including insulin resistance and hyperglycaemia, that may contribute to amyloid formation by increasing IAPP production by the beta-cell. beta-Cell dysfunction, evident as impaired glucose-stimulated insulin secretion and defective prohormone processing and exacerbated by metabolic stress, is also a likely prerequisite for islet amyloid formation to occur in type 2 diabetes. Islet transplants in patients with type 1 diabetes face similar stressors, and are subject to rapid amyloid formation and impaired proinsulin processing associated with progressive loss of beta-cell function and mass. Declining beta-cell mass is predicted to increase metabolic demand on remaining beta-cells, promoting a feed-forward cycle of beta-cell decline.

• 出版日期2012-10